{"id":57254,"date":"2026-03-02T02:20:22","date_gmt":"2026-03-02T01:20:22","guid":{"rendered":"https:\/\/inmuno.es\/index.php\/2026\/03\/02\/toxoplasma-gondii-effector-maf1-blocks-mouse-aim2-inflammasome-activation-by-inhibiting-mtdna-release\/"},"modified":"2026-03-02T02:20:22","modified_gmt":"2026-03-02T01:20:22","slug":"toxoplasma-gondii-effector-maf1-blocks-mouse-aim2-inflammasome-activation-by-inhibiting-mtdna-release","status":"publish","type":"post","link":"https:\/\/inmuno.es\/index.php\/2026\/03\/02\/toxoplasma-gondii-effector-maf1-blocks-mouse-aim2-inflammasome-activation-by-inhibiting-mtdna-release\/","title":{"rendered":"Toxoplasma gondii effector MAF1 blocks mouse AIM2 inflammasome activation by inhibiting mtDNA release"},"content":{"rendered":"<div>\n<p><b>J Immunol<\/b>. 2026 Feb 9;215(2):vkaf360. doi: 10.1093\/jimmun\/vkaf360.<\/p>\n<p><b>ABSTRACT<\/b><\/p>\n<p>Toxoplasma gondii is an obligate intracellular pathogen that can infect most nucleated cell types in rodents and humans. Parasite infection is regulated by inflammasome activation, downstream of Toll-like receptors (TLRs) priming, and interferon \u03b3 (IFN-\u03b3)-mediated activation of immunity inducible GTPases. In vivo, the activation of these pathways overlaps, however, the molecular mechanism of cooperation between IFN-\u03b3 signaling and inflammasome activation has not been rigorously explored during T. gondii infection. Here we show that IFN-\u03b3 is sufficient to prime T. gondii-induced inflammasome activation in murine myeloid cells. The cytosolic DNA sensor absent in melanoma 2 (AIM2) inflammasome plays a dominant role in IL-1\u03b2 release through caspase-1\/11 and ASC in cooperation with NLRP3. Unexpectedly, we found that AIM2 inflammasome activation was not dependent on parasite killing as iNOS-deficiency rescued T. gondii clearance but did not inhibit IL-1\u03b2 release or cell death. Instead, we found that depleting host mitochondrial DNA (mtDNA) blocked IL-1\u03b2 release, suggesting that host DNA is the ligand for AIM2. Moreover, we found that expressing mitochondrial association factor 1 (MAF1I) from the hyper-virulent type I strain in type II T. gondii significantly inhibited the release of mtDNA into the host cell cytosol and reduced inflammasome activation. These data indicate that T. gondii infection in the context of IFN-\u03b3 signaling leads to AIM2 inflammasome activation by host mtDNA, a process that is competitively inhibited by MAF1I-mediated mitochondrial recruitment to the parasitophorous vacuole.<\/p>\n<p>PMID:<a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/41764738\/?utm_source=SimplePie&amp;utm_medium=rss&amp;utm_content=2985117R&amp;ff=20260301202012&amp;v=2.19.0.post6+133c1fe\">41764738<\/a> | DOI:<a href=\"https:\/\/doi.org\/10.1093\/jimmun\/vkaf360\">10.1093\/jimmun\/vkaf360<\/a><\/p>\n<\/div>","protected":false},"excerpt":{"rendered":"<p>J Immunol. 2026 Feb 9;215(2):vkaf360. doi: 10.1093\/jimmun\/vkaf360. ABSTRACT Toxoplasma gondii is an obligate intracellular pathogen that can infect most nucleated cell types in rodents and humans. Parasite infection is regulated by inflammasome activation, downstream of Toll-like receptors (TLRs) priming, and interferon \u03b3 (IFN-\u03b3)-mediated activation of immunity inducible GTPases. In vivo, the activation of these pathways &#8230; <a title=\"Toxoplasma gondii effector MAF1 blocks mouse AIM2 inflammasome activation by inhibiting mtDNA release\" class=\"read-more\" href=\"https:\/\/inmuno.es\/index.php\/2026\/03\/02\/toxoplasma-gondii-effector-maf1-blocks-mouse-aim2-inflammasome-activation-by-inhibiting-mtdna-release\/\" aria-label=\"Read more about Toxoplasma gondii effector MAF1 blocks mouse AIM2 inflammasome activation by inhibiting mtDNA release\">Read more<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[42,71],"tags":[],"class_list":["post-57254","post","type-post","status-publish","format-standard","hentry","category-publicaciones","category-the-journal-of-immunology"],"_links":{"self":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/57254","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/comments?post=57254"}],"version-history":[{"count":0,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/posts\/57254\/revisions"}],"wp:attachment":[{"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/media?parent=57254"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/categories?post=57254"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/inmuno.es\/index.php\/wp-json\/wp\/v2\/tags?post=57254"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}